Usually beginning as a benign process of a normally functioning immune system, immune complex formation may initiate injury to various organs and tissues. The activation of complement, a normal blood product, by CICs can lead to a series of destructive events, including cell lysis and deposition of CICs on various vessel walls, cell membranes, etc. The antigens responsible for initiating such a pathogenic immune response are often unknown in specific clinical practice, but may be microorganisms, tumors or, indeed, the body's own tissues. Infectious diseases such as hepatitis B can also be accompanied by immune complex disease. CICs are so far reaching in relationship to diagnosis and measuring the efficiency of therapy in various clinical situations such that, in the last 10 years, more than 40 assays have been developed to detect and quantify such immune complexes in human pathologic fluids. The brochures prepared by industry leaders (e.g., Maryland Medical Laboratory brochure, designated 4/87 or Roche Biomedical Laboratories brochure, prepared in 1987), attest to the magnitude of the chemical problems secondary to enhanced CIC production in man. Table 1 of the Maryland Medical Laboratory brochure is hereby incorporated by reference to indicate the range of the diseases associated with CICs.
CICs may actually contain virus particles as in the case of virus inclusion of the AIDS virus itself in CICs of AIDS patients (Morrow et al, Clin. Immunology and Immuno Pathology, Vol. 40, p. 515, 1986). The CICs, especially if present in high concentrations, may actually cause an immunosuppressive effect and can even cause blockade of the body's vital reticuloendothelial system (see references cited in Morrow et al). Thus, circulating ICs may be one of the reasons for the abnormal functioning of monocytes-macrophages in many human and animal diseases, including AIDS. Accordingly, it is clear that, while formation of "small" amounts of IC may be part of a normal pathophysiological response to disease, inappropriate synthesis of IC will cause and/or accelerate various diseases.
Immune complex formation is a useful parameter particularly in assessment of rheumatic diseases, such as rheumatoid arthritis and systemic lupus. Specifically, elevated levels of immune complexes seem to track disease activity in many patients over time.
Among the methods used to evaluate CICs in man is the assay for the CR1 receptor, a glycoprotein that binds certain fragments (notably C3G and C4G) of the complement system. Erythrocytes or red blood cells (RBCs) carry on their surface the majority of CR1 receptors in the body's circulation. CR1 appears to endow RBCs with the capacity to clear CICs by transporting them to the liver where they are removed by local monocytes/macrophages (see Tausk et al, J. Clin. Investigation, Vol. 78, p. 977, 1986, and articles cited therein). Various diseases involving autoantibodies and CIC, such as arthritis, leprosy and AIDS, are associated with low levels of erythrocyte CR1.
Two different designators for the AIDS virus exist; LAV is the designator for the AIDS virus isolated at the Pasteur Institute, Paris, France, and HTLV-III is the designator for the AIDS virus isolated at the National Institute of Health, Bethesda, Md., U.S.A. Frequently in this text, the AIDS virus will be referred to generically or designated HTLV-III or LAV without intending to differentiate between them. Furthermore, the term "AIDS virus" in the specification and claims includes any and all other viruses which may be associated with producing AIDS, whether yet isolated or not.